Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. I: Studies in rat in vivo

The incorporation of L-4,5-[³H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL, HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained in the incorporation of simultaneously injected 1,5[¹⁴C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty acids and cholesterol from³H₂O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis.     

Lipid metabolism and tissue composition in Atlantic salmon (Salmo salar L.)—Effects of capelin oil, palm oil, and oleic acid-enriched sunflower oil as dietary lipid sources

Triplicate groups of Atlantic salmon (Salmo salar L.) were fed four diets containing different oils as the sole lipid source, i.e., capelin oil, oleic acid-enriched sunflower oil, a 1∶1 (w/w) mixture of capelin oil and oleic acid-enriched sunflower oil, and palm oil (PO). The β-oxidation capacity, protein utilization, digestibility of dietary fatty acids and fatty acid composition of lipoproteins, plasma, liver, belly flap, red and white muscle were measured. Further, the lipid class and protein levels in the lipoproteins were analyzed. The different dietary fatty acid compositions did not significantly affect protein utilization or β-oxidation capacity in red muscle. The levels of total cholesterol, triacylglycerols, and protein in very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and plasma were not significantly affected by the dietary fatty acids. VLDL, LDL, and HDL fatty acid compositions were decreasingly affected by dietary fatty acid composition. Dietary fatty acid composition significantly affected both the relative fatty acid composition and the amount of fatty acids (mg fatty acid per g tissue, wet weight) in belly flap, liver, red and white muscle. Apparent digestibility of the fatty acids measured by adding yttrium oxide as inert marker, was significantly lower in fish fed the PO diet compared to the other three diets.     

Changes in high density lipoprotein subfraction lipids during neutral lipid transfer in healthy subjects and in patients with insulin-dependent diabetes mellitus

While it is known that the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apo B-containing lipoproteins is increased in patients with diabetes, the extent to which the various lipoprotein fractions engage in neutral lipid exchange and the magnitude to which triglyceride (TG) is translocated is not known. To examine in greater detail neutral lipid net mass transfer in diabetes, the HDL subfractions and the apo B-containing lipoproteins were separated, and the net mass transfer of CE and TG was compared to that of control subjects. In both groups, bidirectional transfer of CE from HDL₃ to very low density lipoprotein (VLDL) + low density lipoprotein (LDL) and of TG from VLDL+LDL to HDL₃, took place, but this process was significantly greater (P<.01) in insulin-dependent diabetes mellitus (IDDM). In contrast, CE and TG accumulated in HDL₂ to a similar degree in normal and IDDM subjects. In recombination experiments with each of the apo B-containing lipoproteins, IDDM VLDL had a greater capacity to facilitate the exchange of core lipids from both IDDM and control HDL₃: on the other hand, LDL from IDDM and control subjects both donated TG and CE to HDL₂ and affected little change in HDL₃. These findings indicate that all the major plasma fractions normally participate in the trafficking of CE and TG among the lipoproteins during neutral lipid transfer and show that the principal perturbation in cholesteryl ester transfer in IDDM involves altered interaction between VLDL and the HDL₃ subfraction.     

The effect of a short term saturated fat diet on the apoprotein composition and radioiodination properties of rat very low density lipoproteins

The effect of a saturated fat diet on the apoprotein composition and radioiodination properties of plasma very low density lipoprotein (VLDL) was studied in rats. After feeding the diet for 10 days, the proportion of¹²⁵I attached to VLDL lipid decreased from 50% (control animals) to 8%, the remainder (92%) being bound to the apoportein components. The decreased lipid labelling was associated with proportional changes in the fatty acid composition of serum and VLDL lipids, the most notable change being a reduction in linoleic acid (30–8%) content which occurred in all the major lipid classes of both serum and VLDL. Analysis of VLDL after radioiodination showed that most of the radioactivity incorporated into the lipid moiety was associated with phospholipid. The proportion of¹²⁵I bound to phospholipid decreased after feeding rats a saturated diet. The proportion of soluble (small molecular weight peptides and arginine rich peptide) to insoluble (B apoprotein) did not alter during the saturated fatty acid dietary regime and no differences in the distribution of soluble proteins were observed. It is concluded that feeding a saturated fat diet to rats for 10 days significantly improved¹²⁵I labelling of the apoprotein moiety while apparently not inducing changes in apoprotein composition.     

Regulation of fatty acid biosynthesis in Ehrlich cells by ascites tumor plasma lipoproteins

Fatty acid biosynthesis in Ehrlich cells in vitro was reduced when very low density lipoproteins (VLDL) isolated from the ascites tumor plasma were added to the incubation medium. The degree of inhibition was dependent on the VLDL concentration. At the VLDL concentrations usually present in the ascites plasma, there was a 30% decrease in biosynthesis as measured by³H₂O incorporation into fatty acids. Analysis of the labeled fatty acids by gas liquid chromatography indicated that this decrease was due to a reduction in fatty acid de novo biosynthesis and that chain elongation actually was increased when VLDL were present. Although ascites plasma low- and high density lipoproteins also produced a concentration-dependent inhibition of fatty acid biosynthesis, their effects were much smaller than those of the VLDL. Studies employing VLDL and radioactive free fatty acids indicated that the cells took up and utilized fatty acids derived from these lipoproteins. When VLDL were present, labeled free fatty acid incorporation into cell phospholipids, cholesteryl esters, and CO₂ decreased, whereas its incorporation into the cell free fatty acid pool increased. By contrast, the cells incorporated only very small amounts of fatty acid from either low- or high density lipoproteins. This suggests that the VLDL exert their inhibitory effect on fatty acid synthesis by supplying exogenous fatty acids to the cells. Presented in part at the AOCS Spring Meeting, Dallas, April 1975.     

Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis: II. Perfused rat liver

Livers from rats with experimental hypoproteinemia induced by aminonucleoside-nephrosis or plasmapheresis were perfused with a [¹⁴C]-labeled amino acid mixture at physiological concentration. Compared to control rats, a significantly increased incorporation of the amino acid label was found in the apolipoproteins of the ultracentrifugally separated very low and high density lipoproteins (VLDL, HDL), and into albumin secreted into the perfusate. However, no increase in the amino acid-derived label was detected in VLDL- or HDL-borne lipids in nephrosis or plasmapheresis. Perfusion with U-[¹⁴C] leucine as a lipogenesis precursor at >10 times higher than physiological concentration resulted in 5-fold increase in the label incorporation into perfusate proteins in nephrosis but only in a slightly significant increase in perfusate lipids. In contrast, the incorporation of a preformed fatty acid, 9,10-[³H] oleate into VLDL and HDL lipids increased 3- to 4-fold in nephrosis. Both with leucine and oleate as precursors, the increments in the label appearing in perfusate proteins or lipids, respectively, were markedly greater than the increases in hepatic tissue proteins or lipids. The results indicate that amino acids are preferentially directed by the liver into the synthesis of circulating apolipoproteins and albumin in hypoproteinemia and do not seem to constitute an important precursor of the lipoprotein lipids. The increased production of apolipoproteins is associated with an increased incorporation of preformed fatty acids into lipoprotein lipids in addition to the previously reported stimulation of hepatic de novo lipid synthesis from precursors other than amino acids.     

Stearic acid modifies very low density lipoprotein lipid composition and particle size differently from shorter-chain saturated fatty acids in cultured rat hepatocytes

Stearic acid as compared to myristate, palmitate, or oleate is poorly incorporated into triacylglycerol, a major lipid component of very low density lipoprotein (VLDL). The present study investigated the effects of these fatty acids on VLDL metabolism in cultured rat hepatocytes. All fatty acids stimulated [2-³H] glycerol incorporation into VLDL lipids and secretion of [³H]-labeled VLDL by hepatocytes. However, the rate of [³H]-labeled VLDL secretion in the presence of nonlabeled stearate (12.8±0.7 pmol/mg protein/4h) was 46, 59, and 22% of that observed for those treated with myristate, palmitate, and oleate, respectively. [1-¹⁴C]Stearate as a substrate was also less effective than other labeled fatty acids to be incorporated into VLDL lipids. Of total VLDL lipids synthesized from [1-¹⁴C] stearate, triacylglycerol accounted for 78% as compared to 88–97% of that derived from palmitate, myristate, and oleate. The amounts of apoB100 and apoB48 were the same in hepatocytes treated with or without exogenous fatty acids. Similarly, the rate of apoB synthesis from [³⁵S] methionine was not affected by exogenous fatty acids. The treatment of cells with various saturated fatty acids increased the particle size of VLDL to different extents. The largest particles of VLDL, with a mean diameter of 79.3±11.9 nm, were seen in the cells treated with stearate, followed by those treated with palmitate and myristate (45.5±9.8 and 38.6±6.8 nm, diameter, respectively). Clearly, hepatocytes treated with stearate secrete less VLDL and produce larger VLDL particles than those treated with shorter-chain saturated fatty acids.     

Effect of protein depletion on the VLDL triacylglycerol secretion and apoprotein synthesis by the perfused liver from pregnant rats

The effect of protein depletion in the pregnant rat on the polyunsaturated fatty acid incorporation into very low density lipoproteins (VLDL) has been investigated. The apoprotein pattern of these particles was determined. In in vivo experiments the amounts of serum and liver triacylglycerol were determined. VLDL were isolated and their apo C concentration calculated. In in vitro experiments the radioactivity of [³H] leucine incorporated into VLDL apoproteins was measured. The results show that protein depletion during pregnancy promotes a drastic increase in serum and liver triacylglycerol. The VLDL isolated from these animals show an increase in the triacylglycerol/protein ratio and a decrease in their content of apo C. Meanwhile, a significant reduction in the [³H]leucine incorporation into apo C peptides by the perfused liver of protein depleted rats was detected. On the other hand, protein deprivation did not affect labeled linoleic and arachidonic acid incorporation into triacylglycerol of the newly secreted VLDL. Taking these results together, let us deduce that a defective VLDL is secreted by the liver of the protein depleted pregnant rats. The abnormal composition of these particles may influence its normal metabolism through their effects on lipoprotein lipase and this fact could affect the normal supply of polyunsaturated fatty acids to the fetus.     

Preparation of fatty acid methyl esters from lipoprotein and macrophage lipid subclasses on thin-layer plates

A simple, accurate, and fast procedure for quantitative analysis of fatty acids (FA) in simple lipid subclasses from different biological specimens is presented. Lipid extracts of isolated plasma lipoproteins (very low, low, and high density lipoproteins; VLDL, LDL, and HDL, respectively) and permanent J774 mouse macrophages were fractionated into lipid subclasses by thin-layer chromatography (TLC) on silica gel 60 plates. Bands comigrating with authentic lipid standards were scraped off under argon and subjected to direct,in situ transesterification with BF₃/MeOH in the presence of the TLC adsorbent. Fatty acid methyl esters were subsequently quantitated by capillary gas chromatography. A comparison of the FA content present in total lipid extracts and in lipid subclasses separated by TLC revealed recoveries ranging from 93 (J774 cell extracts) to 99.7% (LDL). The method described is applicable for the measurement of FA in individual lipid subclasses and was successfully applied to quantitatively analyze the FA composition of the phospholipid, triacylglycerol, and cholesteryl ester fraction derived from VLDL, LDL, and HDL. In J774 lipid extracts, the FA composition of the phospholipid-, monoacylglycerol-, diacylglycerol-, free fatty acid-, triacylglycerol-, and cholesteryl ester fraction was quantitated. In addition we have analyzed the time-dependent loss of the major HDL polyunsaturated fatty acids (18:2, 20:4) in the phospholipid and cholesteryl ester fraction during copper-dependent peroxidation of HDL. We have not encountered analytical problems concerning low FA recoveries from CE-rich lipid extracts as indicated by almost quantitative recoveries of FA in LDL, HDL, and J774 extracts.     

Eicosenoic and docosenoic acid incorporation in serum lipoproteins in rats fed rapeseed oil

Rats were fed rapeseed oil rich in eicosenoic (20∶1) and docosenoic (22∶1) acids for 7 days, and the fatty acid composition of the lipid classes of serum and serum lipoproteins was determined. Concentrations of 20∶1 and 22∶1 acids in the lipid classes were variable, especially among lipoproteins, and were a direct function of the alimentary state of the animal. The results suggest differences in the incorporation of the above acids among the major lipoprotein types and various lipid classes within a given lipoprotein type. The quick partial disappearance of very low density lipoproteins (VLDL) and of low density lipoproteins (LDL) containing 20∶1 and 22∶1 acids upon starvation and the preferential incorporation of these acids in the triacylglycerols of high density lipoproteins (HDL) are discussed.     

Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes

Hepatocytes isolated from female rats meal-fed a high-glucose diet were incubated in Krebs-Henseleit bicarbonate medium containing 16.5 mM glucose,³H₂O, and¹⁴C-labeled amino acids (−)-Hydroxycitrate depressed the incorporation of³H₂O and [¹⁴C] alanine into fatty acids and cholesterol. Incorporation of [U-¹⁴C] leucine into lipids was not affected but incorporation of³H₂O into lipids was decreased significantly by (−)-hydroxycitrate. (−)-Hydroxycitrate depressed the incorporation of radioactivity from [2-¹⁴C]leucine into fatty acids and cholesterol by 61 and 38%, respectively, and stimulated the incorporation of radioactivity from [4,5-³H]leucine 35 and 28%. As [2-¹⁴C]leucine labels the acetyl-CoA pool and [4,5-³H]leucine labels the acetoacetate pool, it was concluded that mitochondrial 3-hydroxy-3-methylglutaryl-CoA is not incorporated intact into cholesterol, and that acetoacetate can be activated effectively in the liver cytosol for support of cholesterol and fatty acid synthesis.     

Regulation of lung surfactant cholesterol metabolism by serum lipoproteins

The isolated perfused rat lung was used as an experimental model in the study of the lipoprotein regulation of surfactant cholesterol metabolism. Addition of low density lipoproteins (LDL) to the perfusion medium at a cholesterol concentration of 0.5 mM had no inhibitory effect on [1-¹⁴C]-acetate incorporation into cholesterol of either the surfactant or residual fractions. Increasing the concentration of cholesterol in the medium to 2.5 mM resulted in significant inhibition of incorporation into cholesterol of both fractions. A similar inhibition resulted when lungs were perfused with 2.5 mM cholesterol in the form of high density lipoproteins (HDL). No inhibition of fatty acid synthesis, measured as incorporation into cholesteryl esters, was observed. The rate of uptake by perfused lung of cholesterol from both high and low density lipoproteins was similar. Competitive binding studies with¹²⁵I-labeled lipoproteins indicated the existence of lung receptors for both classes of lipoprotein. The rate of uptake of the apoprotein moiety of low density lipoproteins was significantly greater than that of high density lipoproteins. These data suggest that lung cholesterol metabolism may be subject to regulation by both low and high density serum lipoproteins.     

Effect of nicotine on lipoprotein metabolism in rats

Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer in smokers. The effect of nicotine on lipoprotein metabolism was studied using rats as the experimental animal. There was a significant increase in the total cholesterol, phospholipids, and triglycerides as well as the amount of lipids associated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in sera of nicotine-treated rats. The incorporation of ³H labeled leucine into the apo B was found to be increased both in the medium and associated cells in the hepatocytes isolated from nicotine-treated rats indicating an increased synthesis and secretion of the apo B containing lipoproteins. This was further confirmed by the higher incorporation of ¹⁴C acetate into total and individual lipids of LDL and VLDL secreted into the medium as well as that associated with different lipids in the cell layer. The activity of lipoprotein lipase in extrahepatic tissues and plasma lecithin cholesterol acyltransferase activity were significantly lower in nicotine-treated rats. These results indicate that nicotine exerts hyperlipidemic effects particularly by increasing the synthesis and secretion of triglyceride-rich lipoproteins. Since nicotine is one of the major hazardous components present in cigarette smoke and tobacco, one can extrapolate that the deleterious effect exerted by nicotine on rats extends to cigarette smokers and those who use other forms of tobacco.     

Studies on the transfer of tocopherol between lipoproteins

The net transfer of labeled α-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) followingin vitro addition of [3,4-³H]all rac-α-tocopherol to plasma, or ii) from plasma obtained 12–16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4′R,8′R-α-[5,7-(C²H₃)₂]tocopheryl acetate and 2S,4′R′,R-α-[5-C²H₃]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37°C. No discrimination between stereoisomers of α-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (>60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observedin vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the %HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r²=0.37,P<0.05).     

Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia

The fatty acid compositions of plasma cholesteryl esters (CE) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) were isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from the high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters.     

Die Fettsäuren in der Nahrung: Ihre Bedeutung für Serumlipide,Lipoproteine und Atherosklerose

Dietary Fatty Acids: their Impact on Serum Lipids, Lipoproteins and Atherosclerosis There are important new data concerning the influence of dietary fats on serum cholesterol and lipoproteins. Earlier results of US-American authors, expressed in the regression equations of Keys, of Hegsted and their collaborators, have been amply confirmed even by authors who interpret their results differently. More recent results concerning trans-fatty acids, stearic acid, n-3-fatty acids which are not considered in the formulae of Keys and Hegsted could have been predicted from modern biochemistry of fatty acids. There are new results describing the influence of chain length of fatty acids on serum lipids. Recent studies center around the influence of fatty acids on lipoproteins. It appears that n-6-polyenoic fatty acids lower LDL but n-3-polyenoic fatty acids lower VLDL. Within the range of foods, commercially available in central Europe, fatty acids do not influence HDL.     

Plasma lipoproteins and liver lipids in two breeds of geese with different susceptibility to hepatic steatosis: Changes induced by development and force-feeding

Susceptibility to fatty liver in the force-fed goose is partly under genetic control. However, the mechanisms leading to liver steatosis in this avian model are poorly understood, but may involve perturbation in hepatic lipoprotein synthesis. Plasma lipoproteins were fractionated by density gradient ultracentrifugation from plasma of geese differing in their susceptibility to liver steatosis (Landes breed, highly susceptible; Rhine breed, partly resistant). The concentrations and chemical compositions of the major lipoprotein classes (VLDL, IDL, LDL and HDL) were characterized at 8, 22 and 27 wk of age and compared to the lipid composition of the corresponding liver. In non-force-fed geese, the lipoprotein profile was typical of birds, with high-density lipoprotein (HDL) predominating (4–5 g/L). However, at 22 and 27 wk of age, very low-density lipoprotein (VLDL) levels were significantly lower in Landes geese suggesting that this breed may possess a lower ability to export liver lipids, which would explain its susceptibility to liver steatosis when overfed. The livers of force-fed geese were specifically enriched in triglyceride, and to a lesser extent, in cholesteryl esters and non-esterified fatty acids as compared to those of control geese of the same age (27 wk). This accumulation of lipids was more pronounced in the Landes breed and was responsible for the higher liver weight in that breed. In both breeds, liver steatosis was accompanied by an increase in plasma levels of HDL (11 g/L), whereas low-density lipoproteins were essentially absent. An increase in VLDL plasma levels occurred in the Landes breed only (2.51 g/Lvs 1.85 g/L in the Rhine breed), and was positively correlated with liver weight. However, VLDL in force-fed geese in both breeds were deficient in triglyceride (28–29% by wt) but enriched in cholesterol (41% by wt). These results indicate that a defect in the incorporation of triglyceride into nascent hepatic VLDL may result in liver steatosis in this species.     

Neue Ergebnisse der klinischen Fettstoffwechsel-Forschung

Recent Results of Clinical Research on Lipid Metabolism Physiology and pathophysiology of serum lipids are primarily related to lipoprotein metabolism. Physico-chemically, lipoproteins can be separated into four classes which interconvert in plasma: chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). VLDL originate from liver and are – as LDL – catabolized in liver. LDL are responsible for the development of severe atherosclerosis. Clinically, we distinguish primary hyperlipoproteinemias, which are genetically determined, and secondary forms of hyperlipoproteinemia. Most of these metabolic disorders are risk factors for atherosclerosis and especially for myocardial infarction. This is demonstrated by pathophysiological and clinical data. In addition, possibilities to influence hyperlipoproteinemia are discussed. There exist a great number of studies of primary and secondary prevention which are discussed with regard to their clinical and epidemiological relevance. In this connexion, the effects of dietary and drug treatment are discussed, and the role of polyunsaturated fatty acids is critically evaluated.     

Net lipid transfer between lipoproteins in fish-eye disease plasma supplemented with normal high density lipoproteins

Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase activity (α-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL₂ or HDL₃ and incubated in vitro at 37 C. After incubation for 0,7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol of the combined VLDL and LDL of fish-eye disease plasma. The present results make it reasonable to conclude that the lack of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer activities.     

Different metabolism of saturated and unsaturated long chain plasma free fatty acids by intestinal mucosa of rats

During fat absorption, unsaturated long chain fatty acids are esterified at a higher rate than saturated fatty acids of similar chain length. This phenomenon has been attributed to differences in the binding affinity of fatty acids to a cytosolic fatty acid-binding protein. As intestinal mucosa utilizes plasma free fatty acids as well, we investigated whether long chainplasma free fatty acids of different degree of saturation are metabolized also at different rates.³H-Palmitic and¹⁴C-linoleic acid complexed to rat serum were injected rapidly into a tail vein of fasting rats. One, 2 and 4 min later there was no difference between³H and¹⁴C-radioactivity in intestinal mucosa, suggesting equal initial uptake of the two labeled fatty acids from plasma. Despite their equal uptake, the incorporation of the isotopes into ester lipids was significantly different, however: at 2 min, 53.1±3.9% of³H and 73.8±4.6% of¹⁴C were recovered in ester lipids. Phospholipids and triglycerides accounted for most of the mucosal³H and¹⁴C. At 4 min, a similar distribution of isotopes in intestinal mucosal metabolites was found. These data show that despite equal initial uptake by intestinal mucosa unsaturated long chain fatty acids taken up from plasma are esterified to a higher and oxidized to a lower extent than saturated plasma free fatty acids. Unsaturated plasma free fatty acids, therefore, may provide a more important source of fatty acids for endogenous intestinal lipoprotein lipids than saturated plasma free fatty acids. It is speculated that the fatty acid binding protein might be operative not only in the intracellular transport and metabolism of luminal fatty acids but of plasma free fatty acids as well.